The present invention is directed to processes for the conversion of 3R,4R-4-acetoxy-3-[1R-1-(t-butyldimethylsilyloxy)ethyl]-2-azetidinone to a penem allyl ester of the formula ##STR1## where R is (C.sub.1 -C.sub.5)alkyl or 1-oxo-3-thiolanyl of the formula ##STR2## and R.sup.1 is a conventional hydroxy-protecting group. In particular the invention is directed to the final stages in which an appropriately substituted 2-chloro-2-((2-azetidinon-1-yl)acetate is converted to the compound (I), in part via the intermediate of the formula ##STR3##
The most preferred compound prepared by means of the present process is the compound of the formula (I) which is an approximately 1:1 mixture of diastereoisomers in which R is (cis-1-oxo-3-thiolanyl), i.e., the thiolane ring substituents are cis relative to each other, and R.sup.1 is t-butyldimethylsilyl. The silyl protecting group and allyl ester are readily cleaved to yield the corresponding 5R,6S-6-(1R-1-hydroxyethyl)2-(cis-1-oxo-3-thiolanylthio)-2-penem-3-carboxy late, a compound first described in European Patent Application No. 130025, which further discloses the method of using this compound as an antibacterial agent. The method of synthesis disclosed in EP 130025 is highly versatile, permitting the facile synthesis of a wide variety of analogs. However, for individual compounds, particularly the above preferred cis compound, a more direct synthesis comprising fewer chemical steps is highly desirable.
When R is (C.sub.1 -C.sub.5)alkyl, the intermediates of the formula (I) are likewise converted by conventional hydrolytic methods to other valuable penem antibiotics and/or beta-lactamase inhibitors such as Sch 29482: ##STR4## See Ganguly et al., J. Antimicrob. Chemotherapy. 9, Supplement C, pp. 1-6 (1982).
The present intermediate compounds of the formula (I) wherein R.sup.1 is t-butyldimethylsilyl and R is ethyl, propyl, butyl, isobutyl or t-butyl are known compounds [Leanza et al., Tetrahedron 39, pp. 2505-2513 (1983)].
The present intermediates of the formula (I) are converted to known penem antibiotics (e.g., Ganguly et al., loc. cit.; Hamanaka, European Patent Application No. 130,025; Daniels et al., J. Chem. Soc., Chem. Commun. 1982 pp. 1119-1120; Tanaka et al., ibid., pp. 713-714) according to known methods for the removal of allyl ester protecting groups [e.g., Ganguly et al., loc. cit.; Girijavallabhan et al., Tetrahedron Lett. 22, pp. 3485-3488 (1981); Jeffrey et al., J. Org. Chem. 47, pp. 587-590 (1982)] and for removal of silyl protecting groups [e.g., Hayashi et al., Chem. Pharm. Bull. 29, pp. 3158-3172 (1981)].